Distinct dendritic cell subsets are associated with immune dysfunction and clinical severity in sickle cell anemia

Abstract

Sickle cell anemia (SCA) is characterized by chronic hemolysis, vaso-occlusion, sustained inflammation, immune dysfunction, and increased susceptibility to infections. Molecules released upon hemolysis are recognized by innate immunity shaping adaptive immune responses. Although dendritic cells (DCs) are central to these processes, comprehensive characterization of their subsets and clinical relevance in SCA remains limited. Here, we performed an in-depth immunophenotypic analysis of circulating DC and monocyte subsets in SCA patients, integrating activation status, immunoregulatory molecules, T-cell phenotypes, systemic cytokines, and hematological and biochemical parameters. We identified distinct signatures across DC subsets. Activated type 2 conventional DCs (cDC2), inflammatory DCs (iDCs), and plasmacytoid DC (pDC) clusters were expanded in SCA, while type 1 cDCs (cDC1) were reduced.